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Ayyoob Arpanaei - One of the best experts on this subject based on the ideXlab platform.

Eberhard Scheuch - One of the best experts on this subject based on the ideXlab platform.

  • effects of the p glycoprotein inhibitor clarithromycin on the pharmacokinetics of intravenous and oral trospium chloride a 4 way crossover drug drug Interaction Study in healthy subjects
    The Journal of Clinical Pharmacology, 2019
    Co-Authors: Bayew Tsega Abebe, Claudia Neumeister, Tobias Tadken, Christiane Modess, Danilo Wegner, Tarek Roustom, Hansulrich Schulz, Ulrich Schwantes, Michael Weiß, Eberhard Scheuch
    Abstract:

    : The quaternary ammonium compound trospium chloride is poorly absorbed from 2 "absorption windows" in the jejunum and cecum/ascending colon, respectively. To confirm whether intestinal P-glycoprotein (P-gp) is involved, a 4-period, crossover drug Interaction Study with trospium chloride after intravenous (2 mg) and oral administration (30 mg) without and after comedication of clarithromycin (500 mg), an inhibitor for P-gp, was initiated in 12 healthy subjects. Pharmacokinetics of trospium was evaluated using gas chromatography-mass spectrometry, noncompartmental evaluation, and pharmacokinetic modeling. Trospium chloride was poorly absorbed after oral administration (absolute bioavailability, ∼8%-10%). About 30% of the bioavailable dose fraction was absorbed from the "narrow window". Comedication with clarithromycin increased steady-state distribution volumes by ∼27% (P < .01). Bioavailability was not increased as hypothesized. The geometric mean ratios (90% confidence interval) for area under the plasma concentration-time curve, maximum concentration, and renal clearance accounted for 0.75 (0.56-1.01), 0.64 (0.45-0.89), and 1.00 (0.90-1.13), respectively. The amount of trospium absorbed from the "narrow window" was reduced in all subjects but from the "wider window" in only 9 of them. Bioavailability was strongly predicted by the maximum absorption rate of trospium in the distal "window" (rs2  = 0.910, P < .0001). In conclusion, the P-gp inhibitor clarithromycin significantly increases distribution volumes but not oral absorption of trospium. The amount absorbed from the "narrow window" was lowered in all subjects. However, the extent of all influences seems not to be of clinical relevance.

  • Effects of the P-Glycoprotein Inhibitor Clarithromycin on the Pharmacokinetics of Intravenous and Oral Trospium Chloride: A 4-Way Crossover Drug-Drug Interaction Study in Healthy Subjects.
    The Journal of Clinical Pharmacology, 2019
    Co-Authors: Bayew Tsega Abebe, Claudia Neumeister, Tobias Tadken, Christiane Modess, Danilo Wegner, Tarek Roustom, Hans‐ulrich Schulz, Ulrich Schwantes, Michael Weiß, Eberhard Scheuch
    Abstract:

    : The quaternary ammonium compound trospium chloride is poorly absorbed from 2 "absorption windows" in the jejunum and cecum/ascending colon, respectively. To confirm whether intestinal P-glycoprotein (P-gp) is involved, a 4-period, crossover drug Interaction Study with trospium chloride after intravenous (2 mg) and oral administration (30 mg) without and after comedication of clarithromycin (500 mg), an inhibitor for P-gp, was initiated in 12 healthy subjects. Pharmacokinetics of trospium was evaluated using gas chromatography-mass spectrometry, noncompartmental evaluation, and pharmacokinetic modeling. Trospium chloride was poorly absorbed after oral administration (absolute bioavailability, ∼8%-10%). About 30% of the bioavailable dose fraction was absorbed from the "narrow window". Comedication with clarithromycin increased steady-state distribution volumes by ∼27% (P 

Fatemeh Ajalloueian - One of the best experts on this subject based on the ideXlab platform.

Bayew Tsega Abebe - One of the best experts on this subject based on the ideXlab platform.

  • effects of the p glycoprotein inhibitor clarithromycin on the pharmacokinetics of intravenous and oral trospium chloride a 4 way crossover drug drug Interaction Study in healthy subjects
    The Journal of Clinical Pharmacology, 2019
    Co-Authors: Bayew Tsega Abebe, Claudia Neumeister, Tobias Tadken, Christiane Modess, Danilo Wegner, Tarek Roustom, Hansulrich Schulz, Ulrich Schwantes, Michael Weiß, Eberhard Scheuch
    Abstract:

    : The quaternary ammonium compound trospium chloride is poorly absorbed from 2 "absorption windows" in the jejunum and cecum/ascending colon, respectively. To confirm whether intestinal P-glycoprotein (P-gp) is involved, a 4-period, crossover drug Interaction Study with trospium chloride after intravenous (2 mg) and oral administration (30 mg) without and after comedication of clarithromycin (500 mg), an inhibitor for P-gp, was initiated in 12 healthy subjects. Pharmacokinetics of trospium was evaluated using gas chromatography-mass spectrometry, noncompartmental evaluation, and pharmacokinetic modeling. Trospium chloride was poorly absorbed after oral administration (absolute bioavailability, ∼8%-10%). About 30% of the bioavailable dose fraction was absorbed from the "narrow window". Comedication with clarithromycin increased steady-state distribution volumes by ∼27% (P < .01). Bioavailability was not increased as hypothesized. The geometric mean ratios (90% confidence interval) for area under the plasma concentration-time curve, maximum concentration, and renal clearance accounted for 0.75 (0.56-1.01), 0.64 (0.45-0.89), and 1.00 (0.90-1.13), respectively. The amount of trospium absorbed from the "narrow window" was reduced in all subjects but from the "wider window" in only 9 of them. Bioavailability was strongly predicted by the maximum absorption rate of trospium in the distal "window" (rs2  = 0.910, P < .0001). In conclusion, the P-gp inhibitor clarithromycin significantly increases distribution volumes but not oral absorption of trospium. The amount absorbed from the "narrow window" was lowered in all subjects. However, the extent of all influences seems not to be of clinical relevance.

  • Effects of the P-Glycoprotein Inhibitor Clarithromycin on the Pharmacokinetics of Intravenous and Oral Trospium Chloride: A 4-Way Crossover Drug-Drug Interaction Study in Healthy Subjects.
    The Journal of Clinical Pharmacology, 2019
    Co-Authors: Bayew Tsega Abebe, Claudia Neumeister, Tobias Tadken, Christiane Modess, Danilo Wegner, Tarek Roustom, Hans‐ulrich Schulz, Ulrich Schwantes, Michael Weiß, Eberhard Scheuch
    Abstract:

    : The quaternary ammonium compound trospium chloride is poorly absorbed from 2 "absorption windows" in the jejunum and cecum/ascending colon, respectively. To confirm whether intestinal P-glycoprotein (P-gp) is involved, a 4-period, crossover drug Interaction Study with trospium chloride after intravenous (2 mg) and oral administration (30 mg) without and after comedication of clarithromycin (500 mg), an inhibitor for P-gp, was initiated in 12 healthy subjects. Pharmacokinetics of trospium was evaluated using gas chromatography-mass spectrometry, noncompartmental evaluation, and pharmacokinetic modeling. Trospium chloride was poorly absorbed after oral administration (absolute bioavailability, ∼8%-10%). About 30% of the bioavailable dose fraction was absorbed from the "narrow window". Comedication with clarithromycin increased steady-state distribution volumes by ∼27% (P 

Francisco B. Veiga - One of the best experts on this subject based on the ideXlab platform.

  • Biopolymers and pilocarpine Interaction Study for use in drug delivery systems (DDS)
    Journal of Thermal Analysis and Calorimetry, 2017
    Co-Authors: Marciana Socorro F. Cordeiro, Pedro José Rolim-neto, Camila Maria B. Silva, Amanda Carla Quintas M. Vieira, Laisa L. Fontinele Sá, Flávia Raquel L. Souza, Lívio César C. Nunes, Daniela Nadvorny, Edson Cavalcanti Da Silva Filho, Francisco B. Veiga
    Abstract:

    This work aimed at the investigation of pilocarpine’s Interaction in the association of cashew gum (CG) and chitosan (CH) biopolymers because of mucoadhesive and prolonged release properties of this polymeric system. To elucidate this issue, characterization techniques, such as DSC, TG, XRD, IR, were applied besides DFT B3LYP/6-31++G(d,p) computational calculations. According to this approach, CG interacts with pilocarpine having a protective thermal effect on the drug and CH can reduce its thermal stability. These Interactions occur, preferably, between a carbonyl group from pilocarpine and hydroxyl groups from biopolymers in which hydrogen bonds are involved. Thus, this work was able to identify Interactions between the drug and the biopolymers and how, in a molecular approach, they occur. These results allow for the full understanding of the influence of each biopolymer for future pilocarpine-release systems.